Medications for Impaired Fasting Glucose
Metformin is the recommended first-line medication for impaired fasting glucose (IFG), particularly in patients with fasting glucose 110-125 mg/dL, those with additional risk factors like obesity (BMI >25 kg/m²), or women with prior gestational diabetes. 1, 2
When to Consider Pharmacotherapy
Medication should be considered after lifestyle interventions (targeting 5-7% weight loss and 150 minutes weekly of moderate physical activity) have been implemented, specifically in these high-risk subgroups 2:
- Fasting plasma glucose 110-125 mg/dL (6.1-6.9 mmol/L) - this upper range of IFG carries substantially higher diabetes risk 3, 4
- Women with history of gestational diabetes - metformin shows particular efficacy in this population 3
- Patients with combined IFG and impaired glucose tolerance (IGT) - highest risk group for progression to diabetes 4
- Obese adolescents with fasting hyperinsulinemia and family history of type 2 diabetes - metformin reduces BMI and improves insulin sensitivity 5
Metformin Dosing and Administration
Start metformin 500 mg daily and increase every 2 weeks as tolerated 1. The typical target dose is 1500-2000 mg daily, divided into two doses 2. For patients with eGFR ≥45 mL/min, metformin can be safely initiated; if eGFR is 30-45 mL/min, dose reduction is required 1.
Key Safety Considerations
- Contraindicated in advanced renal insufficiency (eGFR <30 mL/min) and should be used cautiously with impaired hepatic function or heart failure due to lactic acidosis risk 1
- Temporarily discontinue before procedures, during hospitalizations, or acute illness that may compromise renal or liver function 1
- Monitor for gastrointestinal side effects (occurs in ~40% of patients) - reduction or elimination may be necessary for persistent symptoms 1, 5
- Monitor vitamin B12 levels long-term as metformin can cause deficiency 1
Alternative Medication: Acarbose
Acarbose is a second-line option that has been shown to delay or prevent diabetes onset in patients with IGT, though it is less effective than metformin and lifestyle changes 2, 4. Acarbose works by reducing postprandial glucose excursions through inhibition of intestinal alpha-glucosidases 6.
Acarbose Dosing
Start at 25-50 mg three times daily with meals, titrating up to 50-100 mg three times daily based on tolerance 6. The maximum dose for patients >60 kg is 100 mg three times daily 6.
Critical Clinical Decision Points
Do not routinely treat all patients with IFG 100-109 mg/dL with medication - approximately two-thirds of people with prediabetes never develop diabetes, and one-third return to normal glucose regulation 3. The risk-benefit ratio does not favor universal pharmacotherapy in lower-risk IFG.
Reserve metformin for the highest-risk patients and initiate it immediately when they meet diagnostic criteria for diabetes rather than treating borderline prediabetes indefinitely 3. This approach avoids putting patients on lifelong medication when they are not yet at risk for microvascular complications 3.
When Metformin Is Not Tolerated or Contraindicated
If metformin cannot be used due to renal impairment (eGFR <30 mL/min), gastrointestinal intolerance, or contraindications, intensify lifestyle interventions rather than substituting other medications 1. The evidence for other glucose-lowering agents in IFG is insufficient to recommend their routine use outside of established type 2 diabetes 1.
Common Pitfalls to Avoid
- Do not use sulfonylureas for IFG - these agents increase hypoglycemia risk and are not indicated for prediabetes 1
- Do not use insulin for IFG - insulin is reserved for established diabetes with inadequate control on oral agents 1
- Do not ignore cost barriers - metformin is inexpensive and should be the first choice; newer agents lack evidence in IFG and add unnecessary expense 1, 7
- Do not prescribe metformin without concurrent lifestyle counseling - medication is less effective than lifestyle changes and should complement, not replace, diet and exercise interventions 2, 7